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CAS No. : | 1435-49-0 | MDL No. : | MFCD00018119 |
Formula : | C6H3Cl2F | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QSDKXMVGRLVIQV-UHFFFAOYSA-N |
M.W : | 164.99 | Pubchem ID : | 74028 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 36.42 |
TPSA : | 0.0 Ų |
GI absorption : | Low |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.83 cm/s |
Log Po/w (iLOGP) : | 2.12 |
Log Po/w (XLOGP3) : | 3.49 |
Log Po/w (WLOGP) : | 3.55 |
Log Po/w (MLOGP) : | 3.91 |
Log Po/w (SILICOS-IT) : | 3.57 |
Consensus Log Po/w : | 3.33 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.55 |
Solubility : | 0.046 mg/ml ; 0.000279 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.17 |
Solubility : | 0.111 mg/ml ; 0.000672 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.9 |
Solubility : | 0.0208 mg/ml ; 0.000126 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.57 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P210-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P403+P235-P501 | UN#: | N/A |
Hazard Statements: | H227-H315-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
...presented by the following formula (4) which can respectively correspond to the formula (1) can be obtained. (D) Fluorine substituted aromatic compound represented by the formula (4) corresponding to the hydroxy compound wherein X1 is a substituent of the group (a) in the formula(1): ... 2,4,6-trinitrofluorobenzene, 2-cyanofluorobenzene, 3-cyanofluorobenzene, 4-cyanofluorobenzene, 2-chlorofluorobenzene, 3-chlorofluorobenzene, 4-chlorofluorobenzene, 2,4-dichlorofluorobenzene, 2,5-dichlorofluorobenzene, 2,6-dichlorofluorobenzene, 3,4-dichlorofluorobenzene, 3,5-dichlorofluorobenzene, 2,4,6-trichlorofluorobenzene, 2,4,5-trichlorofluorobenzene, pentachlorofluorobenzene, 1,2-difluorobenzene, 1,3-difluorobenzene, ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In chloroform; dimethyl sulfoxide; | Example 32 (+-) cis-1-(3,4-Dichlorophenoxymethyl)-2-aminoindane Hydrochloride (E32) A solution of (+-) cis-1-hydroxymethyl-2-aminoindane (1.0g, 6.1mmol) in dry dimethyl sulfoxide (25ml) was treated with sodium hydride (221mg of an 80% dispersion in oil, 7.3mmol). After stirring for lh at room temperature under argon, <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (0.86ml, 7.3mmol) was added in one portion and stirring continued overnight at room temperature. The mixture was then poured into water (200ml) and extracted three times with diethyl ether. After drying over sodium sulfate, volatiles were removed in vacuoand the residue subjected to column chromatography on silica gel eluding with 5% ethanol in chloroform to afford a brown oil (501mg) which was converted to the HCl salt and crystallized to afford the title compoundas a white solid. m.p. 235-238C dec. (from methanol-diethyl ether). 1 Nmr (CDCl3 delta: 3.05 (1H, dd, J=6,15Hz), 3.40 (1H, dd, J=8,15Hz), 3.73 (1H, m), 3.92 (1H, m), 4.40 (2H, d, J=6Hz), 7.05 (1H, dd, J=3,9Hz), 7.34 (5H, m), 7.54 (1H, d, J=9Hz), 8.62 (3H, br. s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; In tetrahydrofuran; at 20℃; for 1.5h;Heating / reflux; | 4-Hydroxypiperidine (50 g) was added portionwise to a stirred suspension ofpotassium fert-butoxide (1 10.9 g) in THF (900 mL) at room temperature and undernitrogen. The mixture was heated at reflux and l,2-dichloro-4-fluorobenzene (98 g) addeddropwise over 30 min. The mixture was stirred at reflux for another 1 h then cooled downs10 to room temperature, diluted with ethyl acetate (500 mL) and washed with water (500 mL).The organic phase was diluted further with ethyl acetate (500 mL) and extracted with 1Mhydrochloric acid (200 mL). The aqueous extract was adjusted to over pH 10 by additionof a solution of sodium hydroxide and extracted twice with tert-butylmethyl ether (750mL). The organic extracts were dried over magnesium sulfate, filtered and concentrated1 5 under vacuum to yield the sub-title compound as a dark oil which was used as such in thenext step.MS (ESI+ve) 246/248 [M+H]+.H NMR 5 (CDC13) 1.60-1.70 (2H, m), 1.97-2.03 (2H, m), 2.75 (2H, td), 3.15 (2H,dt), 4.29-4.37 (1H, m), 6.78 (1H, dd), 7.00 (1H, d), 7.31 (1H, d). |
Yield | Reaction Conditions | Operation in experiment |
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84% | Method B; 4-(3,4-Dichloro-phenoxy)-2,2,6,6-tetramethyl-piperidine hydrochloric acid salt; A mixture of 4-(2,2,6,6-tetramethyl)-piperidinol (3.15 g 20 mmol), tetrahydrofuran (50 ml), potassium tert-butoxide (6.72 g, 60 mmol) and <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (2.47 ml, 21 mmol) was stirred for 4 h at room-temperature. Water (100 ml) was added and the mixture was extracted with diethyl ether (2 x 50 ml). Hydrochloric acid in ether (6.5 ml, 3.1 M) was added and the hydrochloric acid salt was precipitated and stirred for 10 min, followed by filtration. Yield 5.69 g (84 %). Mp 291C. |
Yield | Reaction Conditions | Operation in experiment |
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EXAMPLE 1This Example illustrates the preparation of l,2-dichloro-4-fluoro-3-methylbenzene. ?-Butyl lithium (75ml, 2.48M in hexanes, Aldrich, 1.1 equivalents) is added over Ih by syringe pump to a solution of l,2-dichloro-4-fluorobenzene (20ml, 28.1g, lequivalents) in anhydrous THF (180ml) at -40 0C, keeping the temperature between -45 C and -40 C. The solution is stirred at -40 0C for 15-30 minutes and then a solution of dimethylsulfate (19ml, 1.2equivalents) in THF (20ml) is added over Ih by syringe pump, keeping temperature between -45 0C and -40 C. The mixture is then stirred at -40 C for 15- 30minutes and then allowed to warm to room temperature. To the solution is then added 5% w/v (or 5% w/w) brine (60ml) followed by aqueous ammonia solution (0.88 NH3,40ml). The mixture is stirred vigorously for 30minutes and then the layers separated. The bottom layer is discarded and the top layer washed with 5% w/v brine solution (100ml) by again stirring for 30minutes and then separating the layers. The top layer is then analysed for product by GC, evaporated to dryness and if necessary purified by distillation. Gas Chromatography Analysis showed 87.1% l,2-dichloro-4-fluoro-3- methylbenzene, 2.1% of a dimethylated fluorodichlorobenzene and 8.0% of a second dimethylated fluorodichlorobenzene.NMR deltacDcis: 2.35 (d, 3H, J = 2.4Hz), 6.92 (t, IH, J = 8.8Hz), 7.27 (ddq, IH, J = EPO <DP n="5"/>8.8, 5.4, 0.6Hz)ppm.MS (GC-MS) M+(EI) = ITS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; sodium hydrogencarbonate; In tetrahydrofuran; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; | Step 2 Preparation of 4-(3,4-dichlorophenoxy)-[1,4']bipiperidinyl-1'-carboxylic acid tert-butyl ester To a solution of potassium tert-butoxide (139.0 g, 1.24 mol) in THF (500 ml) was added a solution of the product of Step 1 (176.2 g, 0.62 mol) in THF (1000 ml). The reaction mixture was stirred 10 minutes before the additon of 3,4 dichlorofluorobenzene (122.8 g, 0.74 mol), this caused a green colouration that subsequently faded. The reaction mixture was then heated at reflux for 90 minutes. The reaction mixture was then cooled to room temperature before the addition of saturated NaHCO3 (1600 ml). The layers were separated and the organic layer stripped to leave an orange semi-solid. The solid was dissolved in DCM (1500 ml) and dried (MgSO4), filtered and the solvent removed. To the resultant solid was added methyl tert-butyl ether (MTBE) (54 ml) and iso-hexane (1000 ml) to give a slurry which was stirred overnight. The slurry was then filtered and washed with isohexane (200 ml) and the solid dried in vacuo at 50 C. to give the sub-titled compound as a pale powder, (211.6 g, 80%; MS: (M+H) 429). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diethyl ether; hexane; | EXAMPLE 32 (+-) cis 1-(3,4-Dichlorophenoxy)-2-methylaminoindane Hydrochloride (E32) The title compound was prepared in a similar manner to Example 26 from (+-) cis 2-methylamino-1-indanol (0.815 g, 5.0 mmol), sodium hydride (0.18 g of an 80% dispersion in oil; 6.0 mmol) and <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (0.99 g, 6.0 mmol). The crude product was purified by chromatography on silica eluding with 0-3% ethanol in diethyl ether. The resulting brown oil (1.3 g) was dissolved in hexane and treated with ethereal HCl to give the hydrochloride salt. Recrystallisation afforded the title compound as a colourless solid, m.p. 238-239 C. (dec) (from methanoildiethyl ether). |
Yield | Reaction Conditions | Operation in experiment |
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In diethyl ether; hexane; | EXAMPLE 30 (+-) cis 2-Amino-1-(3,4dichlorophenoxy)indane Hydrochloride (E30) The title compound was prepared in a similar manner to Example 26 from (+-) cis 2-amino-1-indanol (2.24 g, 15.0 mmol), sodium hydride (0.54 g of an 80% dispersion in oil; 18.0 mmol) and <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (2.97 g, 18.0 mmol). The crude product was purified by chromatography on silica eluding with 0-4% ethanol in diethyl ether. The resulting light brown oil (3.89 g) was extracted into a mixture of hexane and diethyl ether and treated with ethereal HCl to give the hydrochloride salt. Recrystallisation afforded the title compound as a colourless solid, m.p. 214-215 C. (dec) (from methanol/ethyl acetate/diethyl ether). 1 H Nmr (DMSO-d6) delta:3.23 (2H, m), 4.15 (1H, m), 5.91 (1H, d, J=6Hz), 7.15-7.60 (7H, m), 8.48 (3H, br s). |
Yield | Reaction Conditions | Operation in experiment |
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(+/-)-(£)-1-Methylamino-hex-4-en-3-ol (300 mg, 1.55 mmol) was dissolved in DMSO (8 ml_) and cooled on an ice bath. NaH (60% in mineral oil, 140 mg, 3.5 mmol) was added and the mixture stirred for 30 min. followed by addition of <strong>[1435-49-0]3,4-dichlorofluoro-benzene</strong> (760 mg, 4.6 mmol) in DMSO (1 ml). The mixture was stirred for 18 h. at room temperature followed by addition of water and extraction with ethyl acetate (4 x 50 ml_). The combined organic phases were dried (sodium sulfate), filtered and evaporated to give the crude product. Flash chromatography with dichloromethane and a gradient of 5-10% methanol containing ammonia (1%) gave the product as a pale yellow oil. The corresponding salt was obtained by addition of a diethylether and methanol mixture (9:1) saturated with fumaric acid. Yield 120 mg (20%). Mp 100.8-101.8C. |
Yield | Reaction Conditions | Operation in experiment |
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With n-butyllithium; In tetrahydrofuran; hexane; | EXAMPLE V 2,3-Dichloro-6-fluorobenzaldehyde Butyl lithium (48 ml of 1.6M in hexane, 52.3 mmoles) was added with stirring over 1.5 hours under nitrogen to a solution of <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (7.85 g, 47.6 mmoles) in dry tetrahydrofuran (120 ml) at -68. The solution wa stirred at -68 for 2 hours and then N-methyl-N-phenylformamide (6.48 ml) in dry tetrahydrofuran (15 ml) was added over 1.5 hours. After a further 1.5 hours at -68, the reaction mixture was poured into 10% aqueous sulphuric acid and ether. The ethereal layer was separated, washed with brine, dried (Na2 SO4) and evaporated to give the desired aldehyde (8 g). M+ 196/194/192, nmr (CDCl3)delta10.5 (s,H). |
Yield | Reaction Conditions | Operation in experiment |
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2.1 g (34%) | In N-methyl-acetamide; methanol; dichloromethane; water; | EXAMPLE 57 1-(3,4-Dichlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-3-benzazepine oxalate A solution of 7,8-dimethoxy-1-hydroxy-2,3,4,5-tetrahydro-3-benzazepine (3 g, 13.4 mmole) in 25 ml dimethylformamide was slowly dropped into a stirring suspension of sodium hydride (50% oil dispersion, 0.7 g, 14.8 mmole), previously washed with hexane, in 10 ml dimethylformamide. After the addition was completed, the mixture was warmed for one hour at 60 C., then was cooled and a solution of <strong>[1435-49-0]3,4-dichlorofluorobenzene</strong> (2.4 g, 14.8 mmole) in 10 ml dimethylformamide was added. After stirring two hours at ambient temperature, the reaction mixture was stirred with 400 ml water and was extracted with ethyl acetate. The organic extract was washed with ethyl acetate. The organic extract was washed with water and saturated NaCl and was dried (anhydrous MgSO4), filtered and evaporated to 7 g of an oil. This oil was purified by HPLC (silica gel, 5% methanol in dichloromethane) to give 2.8 g (57%) of an oil. This oil was converted to the oxalate salt as in Example 1 and was recrystallized from ethyl acetate-methanol to give 2.1 g (34%) of 1,(3-4-dichlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-3-benzazepine oxalate, d 167-168 C. ANALYSIS: Calculated for C18 H19 Cl2 NO3.C2 H2 O4: 52.41%C, 4.62%H, 3.06%N, Found: 52.18%C, 4.53%H, 3.00%N. |
Yield | Reaction Conditions | Operation in experiment |
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a) 1,2-dichloro-3-ethyl-4-fluorobenzene; 1,2-Dichloro-4-fluorobenzene (1.3 mL) was dissolved in THF (10 mL) and the resultant solution was cooled to -78 C. n-Butyl lithium (10M, 1.2 mL) was added dropwise over 5 min. The resultant solution was stirred at -78 C for 5 min then allowed to warm to ca-40 C and held at this temperature for 15 min. The solution was cooled to -78 C and then iodoethane (1.24 mL) was added. The resultant solution was allowed to warm to 10 C. pH7 Buffer was added followed by ethyl acetate and diethyl ether. The phases were separated and the aqueous phase was extracted twice with diethyl ether. The organics were combined, washed with brine, dried, filtered and concentrated to give the title compound, contaminated with diethyl ether and ethyl acetate. (2.37 g). GCMS 97.75% retention time 4.61 min (M+ (EI) 192/194/196; bp 177) (Agilent 6890/5973 GC/MSD HP5-MS column, 30m x 0.25mm with a film thickness of 0.25um, 90-310 C at 30 C/min). 'H NMR No. (CDCl3) (3H, t), 2.84 (2H, qd), 6.92 (1H, t), 7.27 (1H, dd). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 3A The aminoalcohol 2b (64 mg, 0.33 mmol) was dissolved in 1,3-dimethylimidazolidinone (0.5 mL) and treated with potassium tert-butoxide (77 mg, 0.69 mmol). 3,4-Dichlorofluorobenzene (163 mg, 0.99 mmol) was added next and the mixture was heated in a 110 C. bath overnight. After cooling, the reaction mixture was diluted with some methanol and purified on a prep HPLC collecting by mass signal to give 3-1 as the trifluoroacetate salt (7 mg). 1H NMR (300 MHz, CDCl3) delta 9.61-9.80 (br s, 2H), 7.35 (d, J=8.8 Hz, 1H), 7.26 (s, 1H), 7.19-7.23 (m, 1H), 7.14 (d, J=2.8 Hz, 1H), 6.96 (dd, J=7.8, 1.5 Hz, 1H), 6.90 (dd, J=8.9, 2.8 Hz, 1H), 6.79-6.83 (m, 1H), 5.46 (d, J=3.8 Hz, 1H), 4.37 (dd, J=11.5, 8.6 Hz, 1H), 4.30 (dd, J=11.7, 2.9 Hz, 1H), 3.23-3.32 (m, 1H), 3.04-3.12 (m, 1H), 2.73-2.78 (m, 1H), 2.67 (s, 3H). APCI MS m/e: 337.7 ([M+H]+) |
Yield | Reaction Conditions | Operation in experiment |
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With potassium hexamethylsilazane; In toluene; at 60℃; for 16h; | tert-butyl 4-cyano-4-(3 ,4-dichlorophenyl)piperidine- 1 -carboxylate[1346] To a solution of 1 ,2-dichloro-4-fluorobenzene (1.64 g, 10 mmol) in toluene (25 mL) was added tert-butyl 4-cyanopiperidine- 1 -carboxylate (2.10 g, 10 mmol) and KHMDS (0.5 M in toluene) (2.99 g, 15.00 mmol). The reaction mixture was stirred at 60 C for 16 hours and cooled to room temperature. After the addition of IN HC1 (25 mL), the reaction mixture was extracted with EtOAc (3 x 20mL). The combined organic extracts were washed with brine (100 mL), dried over MgS04, filtered, and concentrated. The residue was purified by Prep-TLC (eluted with ethyl acetate: petroleum ether = 1 : 5) to provide Example 141A. LCMS: 255 [M-100]+. | |
With potassium hexamethylsilazane; In toluene; at 60℃; for 16h; | Example 140A tert-butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate To a solution of <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (1.64 g, 10 mmol) in toluene (25 mL) was added tert-butyl 4-cyanopiperidine-1-carboxylate (2.10 g, 10 mmol) and KHMDS (0.5 M in toluene) (2.99 g, 15.00 mmol). The reaction mixture was stirred at 60 C. for 16 hours and cooled to room temperature. After the addition of 1N HCl (25 mL), the reaction mixture was extracted with EtOAc (3*20 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by Prep-TLC (eluted with ethyl acetate: petroleum ether=1:5) to provide Example 140A. LCMS: 255 [M-100]+. | |
With potassium hexamethylsilazane; In toluene; at 60℃; for 16h; | tert-butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-l-carboxylate[255] To a solution of l,2-dichloro-4-fluorobenzene (1.64 g, 10 mmol) in toluene (25 mL) was added tert-butyl 4-cyanopiperidine- 1 -carboxylate (2.10 g, 10 mmol) and KHMDS (0.5 M in toluene) (2.99 g, 15.00 mmol). The reaction mixture was stirred at 60 C for 16 hours and cooled to room temperature. After the addition of IN HC1 (25 mL), the reaction mixture was extracted with EtOAc (3 x 20mL). The combined organic extracts were washed with brine (100 mL), dried over MgS04, filtered, and concentrated. The residue was purified by Prep-TLC (eluted with ethyl acetate: petroleum ether = 1 : 5) to provide Example 140A. LCMS: 255 [M-100]+. |
With potassium hexamethylsilazane; In toluene; at 20 - 60℃; for 16h; | To a solution of <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (1.64 g, 10 mmol) in toluene (25 mL) was added tert-butyl 4-cyanopiperidine-1-carboxylate (2.10 g, 10 mmol) and KHMDS (0.5 M in toluene) (2.99 g, 15.00 mmol). The reaction mixture was stirred at 60 C. for 16 hours and cooled to room temperature. After the addition of 1N HCl (25 mL), the reaction mixture was extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by Prep-TLC (eluted with ethyl acetate: petroleum ether=1:5) to provide Example 141A. LCMS: 255 [M-100]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With lithium hydroxide monohydrate; silver trifluoromethanesulfonate; Selectfluor; In ethyl acetate; at 55℃;Sealed tube; | General procedure: Trifluoroborate (0.50 mmol, 1.0 equiv), LiOH·H2O (25.2 mg, 0.60 mmol, 1.2 equiv), Selectfluor (212 mg, 0.60 mmol, 1.2 equiv), AgOTf (386 mg, 1.5 mmol, 3.0 equiv) were weighed into a 20 mL microwave vial. EtOAc (5 mL) was added, and sealed with a microwave cap and the mixture was allowed to stir at 55 C for 5-15 h. The resulting solution was cooled to room temperature. For the compounds reported with isolated yields (2a, 2b, 2c, 2d, 2e, 2g, 2h, 2j, 2k, 2l, 2m, 2o, 2p, 2t, 2u, 2x, 2v, 2y, 2ab, 2ac, and 2ag) the reaction mixture was diluted with MTBE or hexane (5 mL) and H2O (4.0 mL). Then organic phase was separated, the aqueous phase was extracted with MTBE (2*5 mL). The combined organic phases were dried over anhydrous Na2SO4. The filtrate was concentrated in rotavapor and the residue was purified by column chromatography on Combiflash with hexanes/EtOAc to afford the desired compounds. The volatile and low yielding products were not isolated and their yields were determined only by 19F NMR of the reaction mixture. For the compounds reported with 19F NMR yields, 4-fluorobenzonitrile (0.50 mmol) was added as reference to the reaction mixture, stirred for 5 min, and then diluted with MTBE or hexane (5 mL) and H2O (3.0 mL). The layers were separated and an an aliquote of the organic phase was withdrawn for the 19F NMR measurement in CDCl3. |
Yield | Reaction Conditions | Operation in experiment |
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REFERENCE EXAMPLE 600 Preparation of (3R)-1-(3,4-dichlorophenyl)pyrrolidine-3-ol (3R)-pyrrolidine-3-ol was reacted with <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> in the same manner as Reference Example 590 to yield the titled compound. MS (ESI) m/z: 232/234 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With PdCl(1,4-bis(diphenylphosphino)butane)(C3H5); tetrabutylammomium bromide; potassium pivalate; In N,N-dimethyl acetamide; at 150℃; for 16h;Inert atmosphere; Green chemistry; | General procedure: As a typical experiment, the reaction of the 2-halopyridine (1 mmol), fluorobenzene derivative (2.5 mmol) and PivOK (0.154 g, 1.1 mmol) at 150 C during 16 h in DMA (3 mL) in the presence of PdCl(C3H5)(dppb) (12 mg, 0.02 mmol) (see tables or schemes) under argon affords the arylation product after evaporation of the solvent and filtration on silica gel |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Under N2 at -65C in anhydrous THF (30 mL)Add dropwise to a solution of <strong>[1435-49-0]1,2-dichloro-4-fluorobenzene</strong> (BBB-1) (2 g, 12.12 mmol)LDA (6.67 mL, 2M, 13.3 mmol). After adding,The reaction mixture was stirred at -65 C under N2 for 30 minutes.Adding DMF to the resulting red solution under N2 at -65C(1.77 g, 24.2 mmol) and the resulting mixture stirred at -65 C for 20 minutes. The reaction was quenched with water (50 mL) and extracted with EtOAc (30 mL x 2).The extract was washed with 1 N HCl (30 mL), brine (30 mL),Dry and concentrate on Na2SO4 to produce crude material, which is petroleum ether(30 mL x 3) extraction. The extracts were concentrated in vacuo to provide BBB-2 as a yellow solid (2.2 g, 94%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.9% | With 1,2-bis(N-methylimidazolium)ethane chloroaluminate; at 60℃; for 4h; | Adding 16.5 g (0.1 mol) of 2,4-dichlorofluorobenzene and 475 g (0.4 mol) of CCl to the reaction flask.87.5g of ionic liquid [C2mim][Cl2]-AlCl3, heat up to 60 C and then keep warm for 4 hours; after the reaction is finished, let stand layer and recover the upper layerThe sub-liquid and the lower organic phase were subjected to distillation under reduced pressure to give the desired product, 2, 4-dichloro-5-fluoro-(trichloromethyl)benzene, 24.2 g, Mp: 293 to 294 C, yield: 92.9%. |
Yield | Reaction Conditions | Operation in experiment |
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With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; | General procedure: A mixture of l-fluoro-4-nitrobenzene (297A) (1.42 g, 10 mmol), 4,4-difluoropiperidine hydrochloride (297B) (1.6 g, 10 mmol), and K2CO3 (4.14 g, 30 mmol) in DMF (80 mL) was stirred at 70 C overnight. After cooled down to room temperature, the mixture was diluted with H2O (200 mL) and extracted with ethyl acetate (80 mL x 2). The combined organic layers was washed with brine (200 mL), dried over anhydrous sodium sulfate, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 20% v/v) to afford Compound 297C. LC-MS (ESI) m/z: 243 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63%Spectr. | With tetrakis(acetonitrile)copper(I)tetrafluoroborate; [4,4?-bis(1,1-dimethylethyl)-2,2?-bipyridine-N1,N1?]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; cesium fluoride; In acetone; at 30℃; for 20h;Inert atmosphere; Irradiation; | General procedure: To a 4 ml borosilicate vial, equipped with a stir bar, was added Ir[dF(CF3)ppy]2(dtbpy)PF6 (2.4 mg, 2.1 mumol, 1.0 mol%) (dF(CF3)ppy, 2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine; dtbpy, 4,4'-di-tert-butyl-2,2'-bipyridine)) and an aryl (tetrafluoro)thianthrenium salt (0.200 mmol, 1.00 equiv.). Under N2 atmosphere, Cu(MeCN)4BF4 (94.4 mg, 0.300 mmol, 1.50 equiv.), anhydrous CsF (36.4 mg, 0.240 mmol, 1.20 equiv.) and anhydrous acetone (2.0 ml, 0.10 M) were added into the reaction vial. Subsequently, the vial was capped and placed 5 cm away from two 34 W blue light-emitting diode (LEDs). The temperature was kept at approximately 30 C through cooling with a fan. After being stirred for 20 h, the reaction mixture was diluted with CH2Cl2 (2 ml) and the resulting mixture was filtered through a short pad of Celite using CH2Cl2 (5 ml) as eluent. The filtrate was collected and concentrated by rotary evaporation. The residue was purified by chromatography on silica gel to afford the fluorinated product. Note that for the optimal results, the use of anhydrous CsF is important for the reaction. When CsF was weighed under ambient atmosphere, the yield of the fluorinated product was lower and the yield of the hydrodefunctionalized product was higher. Schlenk techniques can be used to avoid moisture. For convenience, we stored and weighed the CsF in a N2-filled glove box; the reactions can be performed outside a glove box. |
Tags: 1435-49-0 synthesis path| 1435-49-0 SDS| 1435-49-0 COA| 1435-49-0 purity| 1435-49-0 application| 1435-49-0 NMR| 1435-49-0 COA| 1435-49-0 structure
[ 3107-21-9 ]
1,2,3-Trichloro-5-fluorobenzene
Similarity: 0.89
[ 3107-21-9 ]
1,2,3-Trichloro-5-fluorobenzene
Similarity: 0.89
[ 3107-21-9 ]
1,2,3-Trichloro-5-fluorobenzene
Similarity: 0.89
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